Reconsidering Treatment-Resistant Depression

Estimates suggest that only half of the individuals suffering with mental illness receive treatment that results in long-term relief. Antidepressant medications are considered a common, cost-effective treatment method for depression, especially with patients undergoing a new diagnosis. Yet, if a patient does not improve after even one antidepressant treatment, their condition could be elevated to Treatment-Resistant Depression (TRD). 

Historically, psychiatrists needed an easy way to classify patients as those who either responded to the medication prescribed to them, or didn’t. Their symptom relief was tracked according to these medications, leading to the coining of the term TRD being non-inclusive of holistic treatment approaches. Due to the specificity of drugs, different dosages, and durations, there is no universally accepted definition for TRD. 

Hans Schroder, Ph.D., recipient of the 2021 Oscar Stern Strategic Translational Research Award, joined Elissa Patterson, MD, Ph.D, and Laura Hirshbein, MD, Ph.D. of the Department of Psychiatry to examine the implications of TRD. Their recent paper, published in the Social Science & Medicine - Mental Health Journal, focuses on four problems with the history and care related to TRD, and proposes recommendations relative to solving each of these problems. 

Firstly, the definition of TRD must shift toward being inclusive of other, non-biomedical related treatments. “By restricting the definition of treatment to medications, TRD implicitly perpetuates the notion that psychiatric medications should be the first-line (or only) treatment for all types of depression.” In addition to pharmacotherapy, the various psycho-social interventions that are effective in treating depression must also be considered.

Secondly, when considering the current TRD framework, one could concur it focuses the blame for depression largely on the pathology of the brain, ignoring the multi-faceted social and environmental causes for the disease. Shifting the narrative for the etiology of this disease from one that solely originates from the brain to one that is a result of various experiences contextual to one’s life may help change the types of treatment offered to patients.

The third problem the researchers propose is that the label of TRD can escalate treatments to those typically reserved for severe major depression, such as electroconvulsive therapy, when it may not be necessary. Instead, the researchers propose refraining the use of current TRD definition as criterion for offering high-risk treatment, and explore other effective but less risk-intensive treatment options.

Finally, the current TRD framework drives funding for research away from effective treatments and preventative public health interventions. Advocating for more social systems-based research, treatment, and programs can help eliminate the gap in holistic approaches to care. 


The authors conclude with, “There are many pathways to recuperate from depression, and our hope is that updates to the concept of TRD will facilitate broader access to a greater variety of pathways.”​​ 

Paper cited:Schroder, Hans S., Elissa H. Patterson, and Laura Hirshbein. "Treatment-resistant depression reconsidered." SSM-Mental Health 2 (2022): 100081